LC-MS/MS法测定比格犬血浆中红景天苷和酪醇的浓度及其药动学 研究.

Objective:To establish a LC-MS/MS method for simultaneous determination of the concentrations of salidroside and its metabolite/rtyrosol in Beagle dog plasma and also to study their pharmacokinetics. Methods: The plasma samples were extracted by a mixed solution of chloroform, phenol and isoamyl alcohol. Then, they were separated on Shimadzu Shim-pack Velox PFPP column (100 mm X2.1 mm ,1.8). Water (phase A) and methanol containing 20% acetonitrile (phase B) was used as mobile phase, the flow rate was 0.3 ml/min with a gradient elution (0-1 min,12% B; 1-2.5 min,12%-85% B;2.5-3.5 min, 85% B; 3.5~3.6 min ,85% -12% B ;3 .6-5 min ,12% B), and the column temperature was 40 °C. Detections were made by using an electro spray ionization (ESI) source and negative ion multiple reaction monitoring (MRM) of m!z 299 .1今118. 9 (salidroside), m/z 137 .0-105 .9 (p-tyrosol) and m/z 285 .1-122 .9 (internal standard gastrodin). Main pharmacokinetic parameters of salidroside and p-tyrosol were calculated after oral and intravenous injection of salidroside. Results: The calibration curves of salidroside and/rtyrosol showed good linearity within the ranges of 1C-1O 000 ng/ml and 1-1000 ng/ml. The intra-day and inte厂day RSD were all less than 12 .9%. After oral administration, the AUCo-r of salidroside and p-tyrosol were respectively (19 600 士 4 870) and (946 士 188) ng • h • ml--1, AUCo-were respectively (19 700 士 4 880) and (2 280士 1 780) ng • h • ml 1, Ck were (8 890士2 650) and (132 .0士44 .3) ng/ml, &/2 were (1 .85士0 .69) and (40 .3士45 .1) h. After intravenous injection, AUCo-r of salidroside and p-tyrosol were respectively (5 960士882) and (127 .0士32 .4) ng • h • ml 1, AUCo-co were respectively (6 000士887) and (157 .0士31 .6) ng • h • ml--1, ＜-脯 were (9 210士 1 900) and (42 .0士 12 .3) ng/ml, &/2 were (0 .976士0 .156) and (4 .46士2 .42) h, respectively. Conclusion: The method is simple, sensitive and efficient with high specificity and could be used for pharmacokinetics study of salidroside and its metabolite/rtyrosol in Beagle dogs. [ABSTRACT FROM AUTHOR]